The proposed project examines the determinants of synaptic strength in the vertebrate nervous system, using the neuromuscular junction as a model. The thin muscle used (snake transversus abdominis) is highly stereotyped and contains a variety of types of motor synapses, all accessible for microscopic and electrophysiological examination. A recent experimental technique, called synaptic reconstruction, is utilized. The technique permits physiological study of neurotransmitter release from one synaptic bouton, the smallest anatomical component of a chemical synapse. As a result, the present need for statistical inference to characterize one bouton's behavior based on that of a population is obviated. in addition, anatomical methods have been developed to visualize structures associated with processing and release of transmitter within the bouton, and structures associated with transmitter-induced conductance change within the postsynaptic receptor membrane. The project's goal is to learn what pr and postsynaptic structures determine the strength of a synapse, and what modifications of these structures are associated with the regulation, or plasticity, of synaptic strength in adults. This knowledge is essential in understanding why such regulation fails in diseases which attack pre-or postsynaptic cells throughout the nervous system.